Enhancing Vaccine Development
and Production
Efficient Centrifuge Systems for Vaccine Development and Production
Avanti JXN-26
The increasing ability of vaccines to impact quality of
life is fueling demand for ever-better vaccine products,
from new therapeutics for cancer and seasonal influenza,
to aver ting threats of bioterrorism and emerging
diseases. Beckman Coulter, Inc. offers a full continuum
of centrifuge-related products to enhance vaccine
development and production. From initial cell clarification
to inactivated viral purification or splitting, Beckman
Coulter, Inc. has the perfect centrifuge for your laboratory.
Drawing on more than 6 decades of expertise, our full
line of centrifugation products delivers quality separations
in a short amount of time. Whether you are focused
on viral, bacterial, or cell-based vaccines, our centrifuge
technology speeds your processes, improves your
yield, and allows you to achieve demanding development
and production goals. In addition to centrifuges, Beckman
Coulter offers complementary solutions for the vaccine
environment, including automated cell viability analyzers,
flow cytometry solutions, and protein characterization
systems. Consider us your partner in creating and delivering
high-quality vaccine products from beginning to end.
Optima XPN 100
Performance
Our instruments, rotors, tubes, bottles and adapters are
designed to work together as a comprehensive system.
A modular approach satisfies cross-contamination
issues by providing lot-to-lot comparability, which
enables faster time-to-market, reduces pharmaceutical
development costs and ensures optimum dose efficacy,
all with the reliability and long-term commitment you’ve
come to expect from Beckman Coulter. Our instruments
and rotors are designed with the consumer in mind as
researchers want faster speeds, better controlled
temperature and vacuum systems, larger capacities,
and increased ease of use for quicker, more reliable,
higher throughput, and reproducible separations.
Compliance
Ease of Use
The traceability and electronic run records of the
Avanti JXN and Optima XPN software support 21
CFR Part 11 compliant and GLP/GMP environments.
The embedded software tracks a long list of run
parameters, usage histories, rotor cycles and more.
Please see application note CENT-512APP09.14-A for
a more detailed look on how Avanti JXN/Optima
XPN centrifuges support 21 CFR Part 11 compliance.
Beckman Coulter’s intuitive, user-friendly instrument
software makes it easy to program centrifuge runs
from within the laboratory or even remotely. The Optima
XPN/Avanti JXN software provides large digital displays,
a comprehensive set of help options, user programmed
workflows, and printable run reports, all in a touchscreen format. The software systems for both the
Optima XPN and Avanti JXN are consistent with each
other, making it easy for customers to go back and
forth between instruments. Furthermore, our ergonomic
system design enhances operator safety, comfort and
productivity, keeping researchers happy and healthy.
Flexibility
As a global leader in centrifugation, Beckman Coulter
delivers innovative centrifuge solutions that enhance the
productivity, efficiency and compliance of vaccine
facilities worldwide. Beckman Coulter centrifuge
solutions meet your facility’s specific needs throughout
the vaccine process, from research and development
to production and validation. Beckman’s product line
offers an array of optimized centrifuge and rotor systems
that allows researchers to select the best fit for their
vaccine-related needs. An integrated library of centrifuge
instruments, rotors, tubes and accessories enables a
high degree of customization and versatility in the use
of your Beckman Coulter systems, ensuring efficiency,
productivity and safety at each step in the process.
Clean Room Suitability
Beckman Coulter’s BioSafe* centrifuge systems are
equipped with a pharmaceutical-grade sterilizing filter
system which alleviates concerns over unwanted
particles escaping into the vaccine production environment.
Our pharmaceutical-grade sterilizing filters are
manufactured in a controlled environment and undergo
extensive integrity testing. The filter components have
met the specifications for biological tests listed in the
current revision of the United States Pharmacopeia
(USP) for Class VI-121˚C plastics and bacterial retention
in conformance with the applicable requirements of
the FDA Guideline Sterile Drug Products Produced by
Aseptic Processing—Current Good Manufacturing
Practice. Furthermore, the filter system undergoes
tests of cleanliness in accordance with Title 21 of the
U.S. Code of Federal Regulations (CFR) parts 211.72
and 210.3 (b) (6), oxidizable substances, pH, and pyrogens.
Workflow screen capture from Optima XPN.
JCF-Z reorienting gradient rotor for high-throughput
virus and cell isolation.
Exemplary Service
A Powerful Lineup
Our reputation for excellence, quality and customer
service is widely recognized—and is the reason
biological facilities around the world look to us for
answers to their centrifugation challenges. Our centrifuge
technology for vaccine development and production is
designed to meet the exacting standards required of
the biologics environment. Our technology is backed
by Beckman Coulter’s ISO 9001 Certified Field Service
Organization. Comprised of factory trained and
cer tified engineers, our service operation has a
reputation that is unmatched in the industry. In addition,
we offer Installation Qualification and Operational
Qualification (IQ/OQ), and our knowledgeable customer
service representatives handle your requests promptly
to keep your facility running efficiently.
Beckman Coulter manufactures and supports a long
list of high-performance ultracentrifuges; Table 1
is not a comprehensive list, but highlights 4 of Beckman
Coulter’s most popular centrifuges for vaccine
development and accompanying commonly-used rotors
in vaccine production. Many rotors are interchangeable
among centrifuge series’. Additionally, Beckman Coulter
offers HarvestLine single-use centrifuge bottle liners that
provide a significant improvement in the centrifugation
of biological material. HarvestLine System liners eliminate
time-consuming manual scraping of harvested solids from
labware and enhance operator biosafety. HarvestLine
liners can be sterilized (gamma irradiation) and frozen
to facilitate your production process.
Table 1. Beckman Coulter Centrifuges and Accompanying Rotors for Vaccine Production.
Centrifuge Series
Rotor
Specifications
Ti-15 Zonal
Max. Speed: 32,000 rpm
Capacity: 1,675 mL
Max. Flow Rate: 50 mL/min
SW-32 Ti
Max. Speed: 32,000 rpm
Capacity: 231 mL
Rate-zonal separation of particles
CF-32 Ti Continuous Flow
Max. Speed: 32,000 rpm
Capacity: 430 mL
Flow Rate: 150 mL/min
High-throughput isolation of large viruses
and bacteria
Type 45 Ti Fixed Angle
Max. Speed: 45,000 rpm
Capacity: 564 mL
Rate-zonal separation of particles
JLA-8.1000 FIxed-Angle
Max. Speed: 5,000 rpm
Capacity: 6,000 mL
Large-volume processing of cells, viruses,
and precipitates
JLA-9.1000 Fixed-Angle
Max. Speed: 9,000 rpm
Capacity: 4,000 mL
Large-volume processing of cells, viruses,
and precipitates
JCF-Z Reorienting Gradient
Max. Speed: 20,000 rpm
Capacity: 1,750 mL
Processing of small or large viruses, bacteria,
and/or whole cells
JCF-Z Continuous Flow
Standard Pellet Core
Max. Speed: 20,000 rpm
Capacity: 1,900 mL
High-throughput isolation and concentration
of viruses and bacteria
JS-5.0 Swinging Bucket
Max. Speed: 5,000 rpm
Capacity: 9,000 mL
Cell harvesting with very high throughput
JS-4.2 Swinging Bucket
Max. Speed: 4,200 rpm
Capacity: 6,000 mL
Rapid pelleting of large quantities of cells,
cell debris, and precipitates
JE-5.0 Elutriator
Max. Speed: 5,000 rpm
Gentle, yet powerful technique for
harvesting large populations of viable cells
Optima XPN
Avanti JXN-26
Avanti J-HC
J6-MI
Vaccine-Related Applications
Efficient isolation of subcellular particles
and antigens
UPSTREAM
Embryonated
Chick Eggs
DOWNSTREAM
1st Inactivation
(Formalin)
Filtration
Inoculation
Concentration
Incubation
Zonal Centrifugation
Detergent
Fragmentation
Candling
Centrifugation
Chilling
Overnight
Harvest (Pool
Allantoic Fluid)
2nd Inactivation
(Formalin)
UF Diafiltration
Sterile Filtration
Clarification
Fig. 1. Typical workflow for egg-based influenza vaccine manufacturing.1
Final Concentrate
Product
Vaccine Development Workflow
and Beckman Coulter
There are two main types of vaccine development:
egg-based and cell-based. Figure 1 demonstrates a
typical workflow for egg-based influenza vaccine
manufacturing1. The upstream process starts with
acquiring embryonated eggs from biosecure flocks,
which are subsequently inoculated and incubated for
several days to allow the virus to sufficiently multiply.
The eggs are then candled to ensure there are no
cracks and then chilled overnight. The next day, the
allantoic fluid is harvested and clarified by the
appropriate means of centrifugation, depending on the
required volumes for production. The Avanti JXN-26
is a perfect complement to your workflow in this step,
providing ample volume and more than enough speed.
The virus is then inactivated by chemical means, filtered,
and concentrated. Zonal centrifugation is now performed
to separate the virus from other contaminating
particles by size and shape in a sucrose solution. Here,
the Optima XPN can be utilized, capable of speeds
fast enough to ensure proper separation. The virus is
recovered and split by detergent to solubilize the viral
membrane, and clarified again by centrifugation to
remove large contaminants. Researchers should again
take advantage of the Optima XPN in this step. The
subunit hemagglutinin and neuraminidase proteins are
isolated, inactivated by a second round of formalin, and
ultrapurified and concentrated by filtration.
Most egg-based vaccine development protocols call for
3 to 5 centrifugation steps at varying speeds and with
different volumes depending on production demands.
The protocol lasts around 7 days with further validation,
formulation, quality control, and lot release following
the purification procedure.
Beckman Coulter centrifuges are compatible with both
egg-based and cell-based vaccine development
laboratories. Many potential advantages exist with
cell-based vaccine development including the lack of
dependence on eggs for global production. Additionally,
the procedure is more reproducible, standardized, and
potentially faster.2,3 The downstream process of cell-based
vaccine development is similar to egg-based manufacturing,
requiring rounds of centrifugation, inactivation, and
filtration. Upstream, the process starts by culturing
frozen, preserved cells in an incubator at 37˚C in small
volumes. The culture is scaled-up and after reaching
a specific density of cells, seed virus is added to the
cell-containing bioreactor, such that the virus infects
the cell lines and multiplies. The virus is subsequently
harvested and clarified by centrifugation.
Vaccine production requires sophisticated instruments
performed by cutting-edge researchers. Beckman
Coulter is a world leader in innovative centrifuges
and here to help your laboratory select the right
equipment to generate the most efficient workflow.
Author
Chad Schwartz, PhD, Senior Application Scientist
Beckman Coulter, Inc., Life Sciences, Indianapolis, IN USA
References
1.Matthews J T. Egg-Based Production of Influenza Vaccine: 30 Years of
Commercial Experience. The Bridge. 17–24: (Fall 2006).
2.International Federation of Pharmaceutical Manufacturers & Associations.
Cell-Culture Based Vaccine. 2014. http://www.ifpma.org/resources/influenzavaccines/influenza-vaccines/cell-culture-based-vaccine.html
3.Dormitzer P R et al. Synthetic Generation of Influenza Viruses for Rapid
Response to Pandemics. Sci Transl Med. 5; 185ra68: (2013). doi: 10.1126/
scitranslmed.3006368
*BioSafe and BioSafety are terms intended to describe the enhanced biocontainment features of our products.
© 2015 Beckman Coulter, Inc. All rights reserved. Beckman Coulter, the stylized logo, Avanti, and Optima are trademarks
of Beckman Coulter, Inc. and are registered with the USPTO. HarvestLine is a trademark of Beckman Coulter, Inc. All other
trademarks are the property of their respective owners.
For Beckman Coulter’s worldwide office locations and phone numbers, please visit “Contact Us” at www.beckmancoulter.com
CENT-751APP01.15-A